PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2′s mitochondria translocation

被引：61

作者：

Hou, Xu ^{[1
]}

Liu, Yaohua ^{[1
]}

Liu, Huailei ^{[1
]}

Chen, Xin ^{[1
]}

Liu, Min ^{[2
]}

Che, Hui ^{[3
]}

Guo, Fei ^{[3
]}

Wang, Chunlei ^{[1
]}

Zhang, Daming ^{[1
]}

Wu, Jianing ^{[1
]}

Chen, Xiaofeng ^{[1
]}

Shen, Chen ^{[1
]}

Li, Chenguang ^{[1
]}

Peng, Fei ^{[1
]}

Bi, Yunke ^{[1
]}

Yang, Zhuowen ^{[4
]}

Yang, Guang ^{[1
]}

Ai, Jing ^{[3
]}

Gao, Xin ^{[5
]}

Zhao, Shiguang ^{[1
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin, Heilongjiang Pr, Peoples R China

[2] Beijing Univ Chinese Med, Coll Basic Med, Beijing, Peoples R China

[3] Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Dept Pharmacol, Harbin, Heilongjiang Pr, Peoples R China

[4] Harbin Med Univ, Affiliated Hosp 1, Dept Endocrinol, Harbin, Heilongjiang Pr, Peoples R China

[5] KAUST, Comp Elect & Math Sci & Engn Div, Thuwal, Saudi Arabia

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

中国国家自然科学基金;

关键词：

ENDOPLASMIC-RETICULUM STRESS; GLIOBLASTOMA CELLS; APOPTOSIS; PATHWAY; CANCER; HYPOXIA; ACTIVATION; AUTOPHAGY; ATTENUATION; GLYCOLYSIS;

D O I：

10.1038/srep09065

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.

引用

页数：9

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